Studies On The Biological Function And Relevant Mechanism Of OCIAD1 In The Pancreatic Cancer

Pancreatic cancer(panreatic cancer) is one of the most common malignant tumors in China, is also a kind of malignant tumor with poor prognosis. The mortality after 2 years of disease accounts for the first in the common cancer. Every year tens of thousands of patients in C hina died of pancreatic cancer. Pancreatic cancer aways has being threat our national health. And in recent years, the incidence of pancreatic cancer is increasing. Every year in the world more than 200000 people died of pancreatic cancer. Among them, the developed countries are with highest morbidity and mortality. In the United States, Pancreatic cancer ranked fourth in all causes of cancer death, more than 28000 cases of pancreatic cancer were diagnosed each year. In Japan, it ranks fifth the causes of cancer death, more than 20000 new cases each year. In developing countries, the incidence of pancreatic cancer also has been increasing year by year. Due to the mortality of pancreatic cancer is very strong, morbidity is basically consistent with mortality. Surgical resection is the main treatment for pancreatic cancer, 5 year survival after surgical resection for pancreatic cancer is less than 20%, postoperative overall survival time is less than 2 years. The characteristic of metastasis and recurrence of pancreatic cancer is the key factor. According to the report, 1 year after radical resection of pancreatic cancer, the postoperative recurrence rate is as high as 60%. Therefore, the in-depth study of pancreatic cancer metastasis and recurrence mechanism and actively explore effective treatment measures is an urgent need to resolve important issues to the diagnosis and treatment of pancreatic cancer. But the pancreatic cancer diagnosis is often late, many patients lost the chance of operation. The diagnosis and treatment of pancreatic cancer is awaya the hot spot in cancer research.OCIAD1(ovarian cancer immunity antigen domain protein 1) gene located on chromosome 4P11. This gene consists of 9 exons and 8 introns, composed of transcription and translation of OCIAD1 produced by the 2 amino acid sequence fragment, the long fragment contains 245 amino acids(27.6Kda), short fragment contains 208 amino acid(20.7Kda), it is a type 1 transmembrane protein, highly conserved in evolution. It participates in cell recognition, cell adhesion, physiological and pathological processes and intracellular signal transduction and plays a important role in cytoskeleton formation. Recently, studies have found that the overexpression of OCIAD1 in ovarian cancer, thyroid cancer can improve the function of integrins and cell extracellular matrix interactions between migration and metastasis, thereby regulated cells in cancer. In the second colonization experiment of ovarian cancer cells, using RNAi technology to inhibit expression of COIAD1, the function of LPA induced collagen 1 and integrin 10/11 adhesion is reduced. We use gene chip technology, semi quantitative PCR, Western Blot and other methods and find the expression of OCIAD1 in pancreatic carcinoma was significantly higher than adjacent, the expression in poorly differentiated pancreatic cancer cells than in well differentiated. Regulation of the expression of OCIAD1 can significantly affect the migration of pancreatic cells, further study found that OCIAD1 may play roles by target ATM(ataxia telangiectasia-mutated) to affect the migration of pancreatic cancer, suggesting that OCIAD1 gene plays an important role in the development of pancreatic cancer. The results are expected to provide a new target for the diagnosis of pancreatic cancer, for treatment and prognosis.Part 1 The expression and clinical significance of OCIAD1 in pancreatic carcinomaObjective Detecte OCIAD1 expression in the fresh tissue of patients with pancreatic carcinoma, verify and clarify its clinical significance. Through bioinformatics analysis, verificate the abnormal expression of OCIAD1 in pancreatic cancer, further detecte the abnormality expression of OCIAD1 vin the cell lines of pancreatic cancer, and compare with the housekeeping gene.Methods The method of Western blot was used to detect the expression level of OCIAD1, in 16 continuously enrolled cases who underwent radical resectio n of pancreatic cancer from Mar 2013 to Sep 2013, these patients were paired pancreatic cancer tissue and paracancerous tissues. to study the expression of target gene, combined with clinical data, Analyze the relationship between expression and clinical d ate.ues biological information analysis in R computer language and GSEA analysis in gene chip of pancreatic cancer to analyze the normal and abnormal expression of genes, verification of the high expression. Further verificate the expression OCIAD1 and housekeeping gene in 22 strains of pancreatic cancer cell line.Results The protein level confirmed OCIAD1 in pancreatic cancer tissue was overexpressed through collected clinical fresh pancreatic cancer tissue with Western blot from. C linical data analysis found the expression of OCIAD1 was close related with clinical tumor malignant degree. Biological information science analysis of gene chip in pancreatic cancer gene expression profile revealed that the high expression of OCIAD1 in pancreatic cancer tissues, and has been verified in 22 pancreatic cancer cell lines.Conclusion OCIAD1 was differentially expressed in pancreatic cancer tissues. The expression of tumor was significantly higher than that in adjacent tissues. The expression of OCIAD1 in pancreatic carcinoma was correlated with the malignant degree of tumor, which may affect the development of pancreatic cancer.Part 2 Effect of OCIAD1 on cell migration of pancreatic cancer cellsObjective To examine the effect of OCIAD1 on the migration of pancreat ic cancer cel s through cytological experiments.Methods Regulate the expression of OCIAD1 in pancreatic cancer cell line As PC-1, Bs PC-1, SW1990 and C APAN, and detect the change of OCIAD1 expression in pancreatic cancer cell proliferation and migration.Results OCIAD1 expression in cancer tissues and pancreatic cancer cell lines expression levels is higher than adjacent tissues and normal pancreatic cell lines. Regulate the OCIAD1 expression in pancreatic cancer cell line, the migration ability of pancreatic cancer cells affected. Upregulated OCIAD1 expression in vitro, the migration ability of pancreatic cancer cells were improved; opposite changes in down regulating the expression of OCIAD1.Conclusion OCIAD1 regulates the proliferation and invasion of pancreatic cancer, and may play an important role in the migration of pancreatic cancer cel s.Part 3 The mechanism of the effect of OCIAD1 in the migration of pancreatic cancerObjective Bioinformatics analysis the OCIAD1 associated kinase in pancreatic cancer, determine the possible role of the kinase, and explore its possible mechanism of action.Methods Select gene chip. Bioinformatics analysis the OCIAD1 associated kinase in pancreatic cancer. Overexpression and interference of OCIAD1 expression in pancreatic cancer cell lines, detect the ATM expression changes. To investigate the mechanism of OCIAD1 and ATM in pancreatic cancer.Results In pancreatic cancer cell lines, OCIAD1 and ALK come into being positive correlation, and ATM into being negative corre lation. Further verification found high credibility in the negative correlation OCIAD1 and ATM. Bidirectional regulation expression of OCIAD1 and ATM in pancreatic cancer cell lines, it is found that OCIAD1 could regulate the ATM level, possibly through the inhibition of cell DNA damage repair pathway, promote pancreatic cancer cell migration, thereby affecting the development and prognosis of pancreatic cancer.Conclusion The expression of OCIAD1 and ATM is negatively correlated, and it may play a role in promoting pancreatic cancer cel s through inhibit the repair of DNA damage.Full text conclusion OCIAD1 in pancreatic cancer tissues with high expression, and is closely related to pancreatic cancer patients with clinical classification stage. Regulating the expression of OCIAD1 can affect the migration of pancreatic cancer cells. The expression of OCIAD1 and ATM was negatively correlated, OCIAD1 regulation ATM level. The overexpression of OCIAD1 promotes the development of pancreatic cancer may be realized through the inhibiting effect of DNA mediated ATM damage repair.